AB0763 Personal approach in axial spondyloarthropathy management
Authors: B. Bugaj, J. Wielinska, J. Swierkot, K. Bogunia-Kubik
Journal: Annals of the Rheumatic Diseases (2022)

Background Spondyloarthropathies (SpAs) are a group of diseases characterized by arthritis in the spine (axialSpA - axSpA) and peripheral joints, and extra-articular symptoms like uveitis, psoriasis or inflammatory bowel diseases. The onset of the disease is difficult to observe. Due to the lack of a pathognomonic test, diagnosis is based on a combination of physical examination, laboratory test and imaging results. The pathogenesis of SpAs is not fully understood, and genetic, environmental and immunological factors are assumed to play a pivotal role. Objectives The study aimed to evaluate selected polymorphisms (ERAP1 rs2287987, ERAP2 rs2549782, TNF rs1800629, TNFRSF1B rs1061622, FCGR2A rs1801274) as prognostic factors of clinical presentations, and response predictors of anti-TNF treatment in axSpA patients. Methods The study enrolled 216 Caucasians: 106 axSpA patients and 110 healthy controls. AS patients were diagnosed according to modified New York criteria, while nr-axSpA patients were diagnosed according to ASAS criteria. Genotyping was performed using LightSNiP assays on the Real-Time PCR Instrument. Clinical data were assessed at baseline, as well as after three and six months of anti-TNF treatment. In addition, information’s about extra-articular symptoms were collected. Results The statistical analysis revealed that TNFRSF1B rs1061622-GG was significantly associated with a higher VAS score at baseline (TT + TG vs GG, p = 0.001), and a higher BASDAI score corrected for the first therapy cycle (X1C BASDAI: TT + TG vs GG, p = 0.005). Moreover, homozygotes were more frequently observed with a lack of BASDAI improvement after six months (X1C BASDAI: TT+GG vs TG, p = 0.045, OR = 2.46, 95%CI 1.00-6.12). ERAP1 rs2287987- GG was more frequently observed with enthesitis (AA vs G+, p = 0.049, OR = 4.636, 95%CI 1.101-21.24). The GG genotype of TNFRSF1B rs1061622 was more common in patients with uveitis than TT variant (GG vs TT, p =0.042, OR = 5, 95%CI 1.08-20). Associations between genetic variants and clinical outcomes were evaluated using laboratory parameters. A lack of the ESR improvement after six months of treatment was more frequently observed within ERAP1 rs2287987-AG (AG vs AA + GG, p = 0.027, OR = 2.72, 95%CI 1.115-6.137) and TNFRSF1B rs1061622- TT (TT vs G+, p = 0.020, OR = 3, 95%CI 1.27-6.9) compared to other genotypes. After three months of therapy, the GG variant of ERAP2 rs2549782 polymorphism was more common among individuals with the lack of ESR improvement than T allele carriers (GG vs T+, p = 0.037, OR = 2.76, 95%CI 1.13-6.72). Differences were also detected between the FCGR2A rs1801274 polymorphism and X1CBASDAI score after six months. The low disease activity (BASDAI &lt; 3) and BASDAI improvement was more frequently observed in patients carrying the A allele than the GG genotype (AA+AG vs GG, p = 0.028, OR = 4.545, 95%CI 1.337-16 and p = 0.012, OR = 6.212, 95%CI 1.683-20.47, respectively). The AG genotype was more common among patients with remission (BASDAI &lt; 2) compared to homozygotes (AG vs AA+GG, p = 0.046, OR = 2.36, 95%CI 1.05-5.13). Conclusion Genetic profiling of patients will help to identify those at risk of high initial disease activity or the presence of extra-articular symptoms. Identifying patients less responsive to treatment may allow selecting a drug with an appropriate efficacy profile. Acknowledgements This work was supported by the grant from Wroclaw Medical University (Poland) STM.A270.20.153. Disclosure of Interests Bartosz Bugaj: None declared, Joanna Wielinska: None declared, Jerzy Swierkot Speakers bureau: For Abbvie, Roche, Lilly, Sandoz, Pfizer, Medac, MSD, Novartis, UCB, Katarzyna Bogunia-Kubik: None declared